| Autor: |
Kara McNamara, Yvonne Latour, Thaddeus Smith, Daniel Barry, Margaret Allaman, Alberto Delgado, M Blanca Piazuelo, Mary Washington, Shilin Zhao, Lori Coburn, Alain Gobert, Keith Wilson |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Gastroenterology. 164:S58 |
| ISSN: |
0016-5085 |
| DOI: |
10.1053/j.gastro.2023.03.109 |
| Popis: |
INTRODUCTION Aconitate decarboxylase 1 (ACOD1; also known as IRG1) is highly expressed in activated macrophages and converts cis-aconitate to itaconate, which contributes to the antimicrobial activity of macrophages. The role of ACOD1 in intestinal inflammation remains unknown. Therefore, we investigated the role of ACOD1 during colitis induced by Citrobacter rodentium (C. rodentium), a murine bacterial pathogen used to model the pathogenesis of enteropathogenic Escherichia coli, and dextran sulfate sodium (DSS) a model of epithelial injury-mediated inflammation. METHODS The GEO database was utilized to examine ACOD1 mRNA levels in ulcerative colitis (UC) and Crohn’s disease (CD) patients, and normal controls. C57BL/6 wild-type (WT) and Acod1–/– mice were infected with C. rodentium for 14 days or given 4% DSS for 5 days and then normal drinking water for 5 days. Mice were weighed daily. Histology was analyzed by H&E staining on colon Swiss rolls using a 0-21 scale for C. rodentium infection and a 0-40 scale for DSS. DNA was extracted from stool to use for 16S microbiome analysis from 5 naïve WT and 5 Acod1–/– mice. RESULTS ACOD1 expression is increased in the colon of UC and CD patients compared to normal controls (GEO GSE16879). Further ACOD1 is significantly increased in active UC compared to inactive (P=0.0256) (GEO GSE75214). C. rodentium-infected Acod1–/– mice lost significantly more body weight compared to infected WT mice (P CONCLUSION While ACOD1 is increased in human IBD tissues, our data indicates that this enzyme has a protective role in experimental colitis. Notably, Acod1 deletion is associated with an altered microbiome. Together our findings suggest that enhancement of ACOD1 activity may represent a new therapeutic strategy for IBD. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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